A New Concept of Immune Specificity Emerges from a Consideration of the Self–Nonself Discrimination

The necessity to make a Self(S)–NonSelf(NS) discrimination is the evolutionary selection pressure for specificity of the immune response. A new definition of paratopic specificity, which is heuristic and generalizable, can be derived from an understanding of this selection pressure. Specificity of the paratope is defined by a Specificity Constant,K,which is the probability that a functional change in recognition will be anti-Self. In an antigen-unselected population,Kis the proportion of cells that are anti-Self. This definition is unique in that it is derived from the function upon which evolution selects, namely the effector output. This paper describes how the concept of a Specificity Constant was derived, how it is estimated, what it can be used to explain, and how it impacts on repertoire and effectiveness of response.